Sodium hypochlorite has a long and well developed history of use as an antiseptic and disinfecting agent. In 1915, Henry Dakin published his classic investigations of antiseptics in the treatment of battlefield wounds encountered in World War I. He evaluated the antiseptic qualities of chemical agents including: phenol, salicylic acid, hydrogen peroxide, iodine, mercuric chloride, silver nitrate and sodium hypochlorite. However, Dakin preferred sodium hypochlorite and recognized not only “its exceptional antiseptic qualities but also the ability of hypochlorite to debride wounds.” See McDonnell, K. J., et al., “Dakin's Solution Revisited,” The American Journal of Orthopedics, July, 1997, pp. 471-3. Sodium hypochlorite solution in succeeding years became known in the medical community as “Dakin's Solution” and was known for its ability to destroy infection causing microorganisms.
While Dakin's solution has been a mainstay in topical antisepsis for almost 90 years, it has fallen into disuse in recent years because of reports of chemical trauma and cytotoxicity as ascertained by in-vitro laboratory tissue culture investigations. In particular, several studies have shown that the commonly used concentrations of sodium hypochlorite can inhibit host defense cells, such as macrophages, leucocytes and fibroblasts and thereby negatively interfere with the healing process. Moreover, laboratory studies have determined that dilute concentrations of Dakin's solution, such as 0.5%, 0.25% and 0.125% w/w, exhibit cytotoxic properties and can cause tissue damage. See e.g., Lineweaver W C, Howard R. Soucy D, et al., “Topical Antimicrobial Toxicity,” Arch Surg, 120:267-270, 1985; Kozol, R. A., et al., “Effects of Sodium Hypochlorite Solution (Dakin's Solution) on Cells of the Wound Module,” Arch Surg, 123:420-423 (1988). It is known that Dakin's solution exhibited cytotoxic properties that inhibited the wound healing process and impaired the host defense mechanism.
Dakin's solution in all concentrations is considered osmotically hypotonic, i.e., it can induce endoosmosis (swelling of tissue and blood cells by an increase in intracellular hydrostatic pressure) possibly causing local tissue stress and edema. Moreover, Dakin's solution diminishes rapidly in antimicrobial effectiveness and chemical activity over the course of its 30 day shelf life limiting its commercial availability to local or hospital pharmacies where it is made fresh to ensure potency. Further, when it is applied topically, it demonstrates a brief duration of action thereby requiring repeated applications to achieve unbroken antisepsis at the wound or burn site.
Based on the work of Lineweaver and others, the use of antiseptic solutions in wounds was discouraged in favor of isotonic saline solution (0.9% sodium chloride) for wound cleansing. The administration of parenteral antibiotics for clinically infected wounds became the standard treatment protocol for all wounds. It was noted, however, in the years following the parenteral antibiotic protocol recommendation that isotonic or normal saline was ineffective in reducing wound bioburden (concentration of microorganisms per gram of tissue), treating a pre-infection state, or treating actual wound infection. Furthermore, a direct link between bacterial wound bioburden and subsequent healing has been established by Dow, G., et al., “Infection in Chronic Wounds: Controversies in Diagnosis and Treatment,” Ostomy/Wound Management, 45(8):23-40 (1999). It has been quantitatively shown that open wounds can maintain a bioburden of approximately 105 microorganisms without the clinical manifestations of infection. A bioburden of greater than 105 represents a significant challenge for local tissue defenses in the wound environment. A clinical wound infection usually results when 106 or more microorganisms per gram of tissue. As a consequence of these studies, the reduction of wound bioburden became a goal of wound therapy.
The emergence of bacterial resistance to a battery of previously effective antibiotic agents, coupled with an inadequate spectrum of action, and ineffective treatment outcomes, exposed the Achilles heel of antibiotics. Subsequently, topical antiseptics and antimicrobials once again emerged as powerful tools in infection control and wound care.
Prior art antiseptics or disinfectants containing chlorine are typically unsatisfactory for topical applications. Bleach solutions typically comprise high concentrations of caustic soda in order to remain stable and avoid decomposition resulting in a high pH that is injurious to skin and wound tissue. Other commonly used antiseptic agents such as Povidone iodine 10%, Hydrogen Peroxide 3% and Acetic Acid 0.25% all exhibit cytotoxic properties or inhibit neodermal formation.
The pH value of antiseptics or disinfectants containing chlorine can be an important factor in the efficacy of a particular antiseptic or disinfectant's antimicrobial activity. The antimicrobial efficacy of hypochlorite has been experimentally shown to be dependent upon pH. It is generally acknowledged that an increase in pH decreases the biocidal activity of chlorine, whereas a reciprocal decrease in pH increases antimicrobial effectiveness. Known antiseptics or disinfectants containing chlorine, including common hypochlorite solutions, typically have high pH values that are not only injurious to skin and wound tissue, as noted above, but are also less effective in reducing wound bioburden as compared to an antiseptic or disinfectant having a lower pH value.
Thus, there is a need for a composition that overcomes the deficiencies of antiseptics, such as Dakin's solution or other chlorine containing disinfectants.